Structure-activity relationship of neuropeptide γ derived from mammalian and fish

This study of relationship between structure and biologic activity was performed using five neuropeptide gamma s [NP gamma; mammalian-NP gamma (M-NP gamma), trout-NP gamma (T-NP gamma), goldfish-NP gamma (G-NP gamma), bowfin-NP gamma (B-NP gamma), and shark-NP gamma (S-NP gamma)]. Circular dichroism (CD) spectra showed that all peptides took random structure in buffer solution. In neutral and acidic liposomes, M-NP gamma, T-NP gamma, B-NP gamma, and S-NP gamma still adopted random structure, while G-NP gamma had an alpha-helical structure. The biologic activity of NP gamma s has been estimated by their effects on the intestinal motility and arterial relaxation. The intestinal motility was investigated with rat duodenum (RD), carp intestine (CI), and guinea-pig ileum (GPI). The arterial relaxing effect was tested with guinea-pig aorta (GPA) and rat mesenteric artery (RMA). In RD, the order of potency compared with the EC50 value was M-NP gamma >> S-NP gamma >> B-NP gamma >> G-NP gamma >> T-NP gamma. G-NP gamma was the most contractile agent in CI. S-NP gamma was the most contractile agent in GPI. Using an arterial relaxing test, the order of potency was G-NP gamma >> T-NP gamma >> B-NP gamma >> S-NP gamma >> M-NP gamma in GPA, and all NP gamma s remarkably reduced relaxing activity in RMA. Despite their structural similarities to NP gamma s, G-NP gamma has high affinity to tachykinin receptor-binding sites in GPA and CI, indicating an alpha-helical structure may have a critical role for receptor binding. However, an alpha-helical structure does not play a critical role in recognizing receptor-binding sites in RD and GPI.